
<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:title>THERMO-RESPONSIVE HYDROGELS FOR INTRAVITREAL INJECTION AND BIOMOLECULE RELEASE</dc:title>
  <dc:creator>Drapala, Pawel</dc:creator>
  <dc:description>In this dissertation, we develop an injectable polymer system to enable localized and prolonged release of therapeutic biomolecules for improved treatment of Age-Related Macular Degeneration (AMD). Thermo-responsive hydrogels derived from N-isopropylacrylamide (NIPAAm) and cross-linked with poly(ethylene glycol) (PEG) poly(L-Lactic acid) (PLLA) copolymer were synthesized via free-radical polymerization. These materials were investigated for (a) phase change behavior, (b) in-vitro degradation, (c) capacity for controlled drug delivery, and (d) biocompatibility. The volume-phase transition temperature (VPTT) of the PNIPAAm-co-PEG- b-PLLA hydrogels was adjusted using hydrophilic and hydrophobic moieties so that it is ca. 33 C. These hydrogels did not initially show evidence of degradation at 37 C due to physical cross-links of collapsed PNIPAAm. Only after addition of glutathione chain transfer agents (CTA)s to the precursor did the collapsed hydrogels become fully soluble at at 37 C. CTAs signi cantly a ected the release kinetics of biomolecules; addition of 1.0 mg/mL glutathione to 3 mM cross-linker accelerated hydrogel degradation, resulting in 100 % release in less than 2 days. This work also explored the e ect of PEGylation in order to tether biomolecules to the polymer matrix. It was demonstrated that non-site-speci c PEGylation can postpone the burst release of solutes (up to 10 days in hydrogels with 0.5 mg/mL glutathione). Cell viability assays showed that at least two 20-minute bu er extraction steps were needed to remove cytotoxic elements from the hydrogels. Clinically-used therapeutic biomolecules Lucentis® and Avastin® were demonstrated to be both stable and bioactive after release form PNIPAAm-co-PEG-b-PLLA hydrogels. The thermo-responsive hydrogels presented here o er a promising platform for the localized delivery of proteins such as recombinant antibodies.</dc:description>
  <dc:description>Ph.D. in Chemical and Biological Engineering, May 2011</dc:description>
  <dc:contributor>Perez-Luna, Victor H.</dc:contributor>
  <dc:date>2011-04-20</dc:date>
  <dc:date>2011-05</dc:date>
  <dc:type>Dissertation</dc:type>
  <dc:format>application/pdf</dc:format>
  <dc:identifier>islandora:6439</dc:identifier>
  <dc:identifier>http://hdl.handle.net/10560/2500</dc:identifier>
  <dc:source>ChBE / Chemical and Biological Engineering</dc:source>
  <dc:source>Illinois Institute of Technology</dc:source>
  <dc:language>en</dc:language>
  <dc:rights>In Copyright</dc:rights>
  <dc:rights>http://rightsstatements.org/page/InC/1.0/</dc:rights>
  <dc:rights>Restricted Access</dc:rights>
</oai_dc:dc>